全文获取类型
收费全文 | 375篇 |
免费 | 39篇 |
专业分类
414篇 |
出版年
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 4篇 |
2019年 | 9篇 |
2018年 | 10篇 |
2017年 | 7篇 |
2016年 | 16篇 |
2015年 | 21篇 |
2014年 | 30篇 |
2013年 | 28篇 |
2012年 | 35篇 |
2011年 | 28篇 |
2010年 | 13篇 |
2009年 | 25篇 |
2008年 | 22篇 |
2007年 | 23篇 |
2006年 | 30篇 |
2005年 | 23篇 |
2004年 | 18篇 |
2003年 | 11篇 |
2002年 | 10篇 |
2001年 | 3篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有414条查询结果,搜索用时 0 毫秒
81.
Luzius Mader Corina S. Rueegg Janine Vetsch Johannes Rischewski Marc Ansari Claudia E. Kuehni Gisela Michel Swiss Paediatric Oncology Group 《PloS one》2016,11(3)
Background
Taking care of children diagnosed with cancer affects parents’ professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment.Methods
As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5–15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5–15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry.Results
We included 394 parent-couples of survivors and 3’341 control parents (1’731 mothers; 1’610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14–5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71–7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13–0.73) and >2 children (OR = 0.48, CI:0.30–0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04–0.36).Conclusion
Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation. 相似文献82.
Claudie Vernotte Corina Solis Ismaël Moya Brigitta Maison Jean-Marie Briantais Bernard Arrio Georges Johannin 《BBA》1983,725(2):376-383
The addition of linolenic acid to thylakoids produces various pH-dependent effects. We have demonstrated a binding site near the Photosystem (PS) II center with a pKa of 6.5: when linolenic acid is unprotonated it induces in the dark a rise of the initial fluorescence level, the latter being similar to the maximum fluorescence obtained during illumination of untreated thylakoids. The comparison of the fluorescence lifetimes in the presence and absence of linolenic acid leads us to conclude that the charge stabilisation on the primary acceptor, Q, is prevented by linolenic acid. A second binding site on the protein carrying B, the secondary acceptor of PS II, has also been demonstrated for linolenic acid. It has a 3-(3,4-dichlorophenyl)-1,1-dimethylurea-type effect both in the protonated and unprotonated forms. Finally, measurements of electrophoretic mobility of the thylakoids indicate several other sites of linolenic acid inclusion with an average pKa of 5.7. At alkaline pH the presence of unprotonated linolenic acid increases the charge density on the membrane. As a result a higher concentration of divalent cations is needed to obtain fluorescence and stacking changes than for untreated thylakoids. The presence, at acidic pH values, of the unprotonated form of linolenic acid leads to the inhibition of cation-induced fluorescence changes, probably by preventing the movement of chlorophyll-protein complexes in the membrane. 相似文献
83.
The mechanism of glucose 6-phosphate–d-myo-inositol 1-phosphate cyclase of rat testis. The involvement of hydrogen atoms 总被引:1,自引:0,他引:1
Comparison of the initial (3)H/(14)C ratios in specifically labelled d-glucose 6-phosphates with the final ratios in myo-inositol produced by glucose 6-phosphate-d-myo-inositol 1-phosphate cyclase from rat testis showed that, during the conversion, the hydrogen atoms at C-1 and C-3 were fully retained, one hydrogen atom was lost from C-6, and that at C-5 was apparently retained to the extent of 80-90%. The loss of (3)H could not be stimulated by addition of unlabelled NADH, and when unlabelled substrate was used (3)H from [(3)H]NADH and [(3)H]water was not incorporated. Treatment of the enzyme with charcoal abolished the activity, and this was restored to 25-50% of the original activity by NAD(+). The charcoal-treated enzyme again apparently gave 85% retention of hydrogen with [5-(3)H]glucose 6-phosphate as substrate in the presence of NAD(+) alone, but the retention was decreased to 65% with excess of NADH. The results are interpreted as indicating that the cyclization proceeds by an aldol condensation in which C-5 is oxidized by NAD(+) in a tightly-bound ternary complex, and that the apparent loss of (3)H when untreated enzyme is used is due to an isotope effect. It is suggested that after treatment with charcoal some exchange of NADH with an external pool may take place. 相似文献
84.
The recombinant congenic strains—a novel genetic tool applied to the study of colon tumor development in the mouse 总被引:4,自引:0,他引:4
Corina J. A. Moen Martin A. van der Valk Margriet Snoek Bert F. M. van Zutphen Otto von Deimling Augustinus A. M. Hart Peter Demant 《Mammalian genome》1991,1(4):217-227
The development of tumors in mice is under multigenic control, but, in spite of considerable efforts, the identification of the genes involved has so far been unsuccessful, because of the insufficient resolution power of the available genetic tools. Therefore, a novel genetic tool, the RC (Recombinant Congenic) strains system, was designed. In this system, a series of RC strains is produced from two inbred strains, a background strain and a donor strain. Each RC strain contains a different small subset of genes from the donor strain and the majority of genes from the background strain. As a consequence, the individual genes of the donor strain which are involved in the genetic control of a multigenic trait, become separated into different RC strains, where they can be identified and studied individually. One of the RC strains series which we produced is made from the parental strains BALB/cHeA (background strain) and STS/A (donor strain). We describe the genetic composition of this BALB/cHeA-C-STS/A (CcS/Dem) series and show, using 45 genetic autosomal markers, that it does not deviate from the theoretical expectation. We studied the usefulness of the CcS/Dem RC strains for analysis of the genetics of colon tumor development. The two parental strains, BALB/cHeA and STS/A, are relatively resistant and highly susceptible, respectively, to the induction of colon tumors by 1,2-dimethylhydrazine (DMH). The individual RC strains differ widely in colon tumor development after DMH treatment; some are highly susceptible, while others are very resistant. This indicates that a limited number of genes with a major effect are responsible for the high susceptibility of the STS strain. Consequently, these genes can be mapped by further analysis of the susceptible RC strains. The differences between the RC strains were not limited to the number of tumors, but the RC strains differed also in size of the tumors and the relative susceptibility of the two sexes. Our data indicate that the number of tumors and the size of tumors are not controlled by the same genes. The genetics of these different aspects of colon tumorigenesis can also be studied by the RC strains. The DMH-treated mice of the parental strains and the RC strains also developed anal tumors and haemangiomas in varying numbers. The strain distribution pattern (SDP) of susceptibility for each of the three types of tumors induced by DMH is different, indicating that development of these tumors is under control of different, largely non-overlapping, sets of genes. Thus, with a single series of RC strains, genes involved in tumorigenesis in various organs and tissues can be studied separately. These results indicate that the novel genetic tool, the RC strain system, offers new possibilities for analysis of the multigenic control of tumor development. 相似文献
85.
86.
New Strategy for Identification of Novel cry-Type Genes from Bacillus thuringiensis Strains 总被引:5,自引:0,他引:5 下载免费PDF全文
We designed five degenerate primers for detection of novel cry genes from Bacillus thuringiensis strains. An efficient strategy was developed based on a two-step PCR approach with these primers in five pair combinations. In the first step, only one of the primer pairs is used in the PCR, which allows amplification of DNA fragments encoding protein regions that include consensus domains of representative proteins belonging to different Cry groups. A second PCR is performed by using the first-step amplification products as DNA templates and the set of five primer combinations. Cloning and sequencing of the last-step amplicons allow both the identification of known cry genes encoding Cry proteins covering a wide phylogenetic distance and the detection and characterization of cry-related sequences from novel B. thuringiensis isolates. 相似文献
87.
88.
Eduardo Castro‐Torres Pedro Jimnez‐Sandoval Sergio Romero‐Romero Alma Fuentes‐Pascacio Laura M. Lpez‐Castillo Corina Díaz‐Quezada D. Alejandro Fernndez‐Velasco Alfredo Torres‐Larios Luis G. Brieba 《The Plant journal : for cell and molecular biology》2019,99(5):950-964
Reactive oxidative species (ROS) and S‐glutathionylation modulate the activity of plant cytosolic triosephosphate isomerases (cTPI). Arabidopsis thaliana cTPI (AtcTPI) is subject of redox regulation at two reactive cysteines that function as thiol switches. Here we investigate the role of these residues, AtcTPI‐Cys13 and At‐Cys218, by substituting them with aspartic acid that mimics the irreversible oxidation of cysteine to sulfinic acid and with amino acids that mimic thiol conjugation. Crystallographic studies show that mimicking AtcTPI‐Cys13 oxidation promotes the formation of inactive monomers by reposition residue Phe75 of the neighboring subunit, into a conformation that destabilizes the dimer interface. Mutations in residue AtcTPI‐Cys218 to Asp, Lys, or Tyr generate TPI variants with a decreased enzymatic activity by creating structural modifications in two loops (loop 7 and loop 6) whose integrity is necessary to assemble the active site. In contrast with mutations in residue AtcTPI‐Cys13, mutations in AtcTPI‐Cys218 do not alter the dimeric nature of AtcTPI. Therefore, modifications of residues AtcTPI‐Cys13 and AtcTPI‐Cys218 modulate AtcTPI activity by inducing the formation of inactive monomers and by altering the active site of the dimeric enzyme, respectively. The identity of residue AtcTPI‐Cys218 is conserved in the majority of plant cytosolic TPIs, this conservation and its solvent‐exposed localization make it the most probable target for TPI regulation upon oxidative damage by reactive oxygen species. Our data reveal the structural mechanisms by which S‐glutathionylation protects AtcTPI from irreversible chemical modifications and re‐routes carbon metabolism to the pentose phosphate pathway to decrease oxidative stress. 相似文献
89.
Role of the 3′-Untranslated Regions of Alfalfa Mosaic Virus RNAs in the Formation of a Transiently Expressed Replicase in Plants and in the Assembly of Virions 下载免费PDF全文
A. Corina Vlot Lyda Neeleman Huub J. M. Linthorst John F. Bol 《Journal of virology》2001,75(14):6440-6449
Alfalfa mosaic virus (AMV) RNAs 1 and 2 encode the replicase proteins P1 and P2, respectively, whereas RNA 3 encodes the movement protein and the coat protein (CP). When RNAs 1 and 2 were transiently expressed from a T-DNA vector (R12 construct) by agroinfiltration of Nicotiana benthamiana, the infiltrated leaves accumulated minus-strand RNAs 1 and 2 and relatively small amounts of plus-strand RNAs. In addition, RNA-dependent RNA polymerase (RdRp) activity could be detected in extracts of the infiltrated leaves. After transient expression of RNAs 1 and 2 with the 3'-untranslated regions (UTRs) of both RNAs deleted (R1Delta/2Delta construct), no replication of RNAs 1 and 2 was observed, while the infiltrated leaves supported replication of RNA 3 after inoculation of the leaves with RNA 3 or expression of RNA 3 from a T-DNA vector (R3 construct). No RdRp activity could be isolated from leaves infiltrated with the R1Delta/2Delta construct, although P1 and P2 sedimented in a region of a glycerol gradient where active RdRp was found in plants infiltrated with R12. RdRp activity could be isolated from leaves infiltrated with constructs R1Delta/2 (3'-UTR of RNA 1 deleted), R1/2Delta (3'-UTR of RNA 2 deleted), or R1Delta/2Delta plus R3. This demonstrates that the 3'-UTR of AMV RNAs is required for the formation of a complex with in vitro enzyme activity. RNAs 1 and 2 with the 3'-UTRs deleted were encapsidated into virions by CP expressed from RNA 3. This shows that the high-affinity binding site for CP at the 3'-termini of AMV RNAs is not required for assembly of virus particles. 相似文献
90.
Ann Smith Jeffrey D. Eskew Corina M. Borza Michael Pendrak Richard C. Hunt 《Experimental cell research》1997,232(2):246
Heme–hemopexin supports and stimulates proliferation of human acute T-lymphoblastic (MOLT-3) cells, suggesting the participation of heme in cell growth and division. MOLT-3 cells express approximately 58,000 hemopexin receptors per cell (apparent Kd20 nM), of which about 20% are on the cell surface. Binding is dose- and temperature-dependent, and growth in serum-free IMDM medium is stimulated by 100–1000 nMheme–hemopexin, consistent with the high affinity of the receptor for hemopexin, and maximal growth is seen in response to 500 nMcomplex. Growth was similar in defined minimal medium supplemented with either low concentrations of heme–hemopexin or iron-transferrin, and either of these complexes were about 80% as effective as a serum supplement. Heme–hemopexin, but not apo–hemopexin, reversed the growth inhibition caused by desferrioxamine showing that heme–iron derived from heme catabolism is used for cell growth. Cobalt-protoporphyrin (CoPP)–hemopexin, which binds to the receptor but is not transported intracellularly [Smithet al.,(1993)J. Biol. Chem.268, 7365], also stimulated cell proliferation in serum-free IMDM but did not “rescue” the cells from desferrioxamine. Furthermore, CoPP–hemopexin effectively competed for the hemopexin receptor with heme–hemopexin and diminished its growth stimulatory effects. In addition, protein kinase C (PKC) is translocated to the plasma membrane within 5 min after heme–hemopexin is added to the medium, reaches maximum activity within 5–10 min, and declines to unstimulated levels by 30 min. Heme–hemopexin and CoPP-hemopexin both augmented MOLT-3 cell growth stimulated by serum. Thus, heme–hemopexin not only functions as an iron source for T-cells but occupancy of the hemopexin receptor itself triggers signaling pathway(s) involved in the regulation of cell growth. The stimulation of growth of human T-lymphocytes by heme–hemopexin is likely to be a physiologically relevant mechanism at sites of injury, infection, and inflammation. 相似文献